Neuregulin-1 type III determines the ensheathment fate of axons
Neuregulin-1 type III determines the ensheathment fate of axons
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DOI：
10.1016/j.neuron.2005.08.017
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发表时间：
2005-09-01
期刊：
影响因子：
16.2
通讯作者：
Salzer, JL
中科院分区：
文献类型：
--
作者：
Taveggia, C;Zanazzi, G;Salzer, JL
决定轴突是否被雪旺细胞包裹或髓鞘化的信号一直难以捉摸。我们现在报告，阈值水平的神经调节蛋白-1（NRG 1）III型轴突决定其ensheathment命运。有鞘轴突表达低水平，而有髓纤维表达高水平的NRG 1 III型。NRG 1 III型缺陷小鼠的感觉神经元鞘化不良，无法髓鞘化;慢病毒介导的NRG 1 III型表达挽救了这些缺陷。表达还将交感神经元的正常无髓鞘轴突转化为髓鞘形成。NRG 1 III型单倍型不足小鼠的神经纤维不成比例地无髓鞘，异常鞘化和髓鞘化不足，传导速度降低。III型是保留在轴突表面的唯一NRG 1亚型，并激活雪旺细胞髓鞘形成所需的PI 3-激酶。这些结果表明，NRG 1 III型的水平，独立于轴突直径，提供了一个关键的指导性信号，决定了鞘的命运轴突。
The signals that determine whether axons are ensheathed or myelinated by Schwann cells have long been elusive. We now report that threshold levels of neuregulin-1 (NRG1) type III on axons determine their ensheathment fate. Ensheathed axons express low levels whereas myelinated fibers express high levels of NRG1 type III. Sensory neurons from NRG1 type III deficient mice are poorly ensheathed and fail to myelinate; lentiviral-mediated expression of NRG1 type III rescues these defects. Expression also converts the normally unmyelinated axons of sympathetic neurons to myelination. Nerve fibers of mice haploinsufficient for NRG1 type III are disproportionately unmyelinated, aberrantly ensheathed, and hypomyelinated, with reduced conduction velocities. Type III is the sole NRG1 isoform retained at the axon surface and activates PI 3-kinase, which is required for Schwann cell myelination. These results indicate that levels of NRG1 type III, independent of axon diameter, provide a key instructive signal that determines the ensheathment fate of axons.